Compositions and methods for preventing infection

ABSTRACT

This invention relates to cholesterol-sequestering agents and methods of using cholesterol-sequestering agents to prevent infection. The compositions of the invention can be used to reduce or prevent maternal to fetal transmission of a microorganism and/or to reduce or eliminate a microorganism present in a blood sample or a blood product.

CROSS REFERENCE TO RELATED APPLICATIONS

Under 35 USC § 120, this application is a divisional application of U.S.application Ser. No. 10/667,727 filed Sep. 22, 2003, now pending; whichclaims the benefit under 35 USC § 119(e) to U.S. Application Ser. No.60/412,399 filed Sep. 20, 2002, now abandoned. The disclosure of each ofthe prior applications is considered part of and is incorporated byreference in the disclosure of this application.

TECHNICAL FIELD

This invention relates to methods and compositions for preventinginfection, and more particularly to methods and compositions usingcholesterol-sequestering agents.

BACKGROUND

Approximately 7,000 human immunodeficiency virus (HIV)-infected womengive birth in the United States each year. Without treatment, aboutone-fourth of them transmit the virus to their children. The anti-HIVdrug zidovudine (AZT), given to HIV-infected pregnant women before andduring childbirth and to their infants after childbirth, reduces HIVtransmission by as much as two-thirds. Treatment with AZT is now thestandard of care in the U.S. for preventing HIV infection in infants.However, additional means are needed for the prevention of maternal tofetal transmission of HIV and other envelope viruses both in the U.S.and worldwide.

SUMMARY

In one aspect, the invention features a method of reducing or preventingmaternal to fetal transmission of a microorganism. The method includesthe steps of: selecting a pregnant individual diagnosed as beinginfected with a microorganism; and administering to the birth canal ofthe individual a composition containing a cholesterol-sequesteringagent, wherein the composition is administered prior to a vaginal birthof a fetus, and wherein an amount of the cholesterol-sequestering agenteffective to reduce or prevent maternal to fetal transmission of themicroorganism remains present in the birth canal during the vaginalbirth.

In another embodiment, the invention features a method of reducing orpreventing maternal to fetal transmission of a microorganism. The methodincludes the steps of: selecting a pregnant individual diagnosed asbeing infected with a microorganism; and administering to the individuala composition containing a cholesterol-sequestering agent, wherein thecomposition is administered to the individual at a site of a surgicalincision for a cesarean section birth of a fetus, and wherein an amountof the cholesterol-sequestering agent that is effective to reduce orprevent maternal to fetal transmission of the microorganism remainspresent at the site during the cesarean section birth.

A “cholesterol-sequestering agent” refers to a compound that binds tocholesterol and extracts and depletes cholesterol from a biologicalmembrane such as a plasma membrane or a membrane of an envelope virus. Acholesterol-sequestering agent preferentially extracts cholesterol fromlipid rafts present in a biological membrane. Thecholesterol-sequestering agent can be, for example, a cyclodextrin. Inone example, the cholesterol-sequestering agent is a beta-cyclodextrinsuch as 2-OH-propyl-beta-cyclodextrin.

“Birth canal” refers to the passageway through which the fetus isexpelled during parturition, leading from the uterus through the cervix,vagina, and vulva.

The microorganism can be, for example, a bacterium (e.g., anthrax orchlamydia), a mycobacterium (e.g., mycobacterium tuberculosis), a virus(e.g., an envelope virus or a non-envelope virus, e.g., a protein coatedvirus such as picorna virus or a papilloma virus), a fungus, or aprotozoan. In some embodiments, the microorganism enters a cell of ahost by endocytosis during at least a portion of its life cycle.

In one example, the microorganism is an envelope virus. The envelopevirus can be, for example, a human immunodeficiency virus (HIV) such asHIV-1 or HIV-2; a human herpes virus (HHV) such as HHV1, HHV2, HHV3,HHV4, HHV5, HHV6, HHV7, or HHV8; a hepatitis virus such as hepatitis Bvirus, hepatitis C virus, or hepatitis D virus; a pox virus such as asmall pox virus or molluscum contagiosum virus; an orthomyxovirus suchas an influenza virus types A, B, or C; a paramyxovirus such as a mumpsvirus or a parainfluenza virus type 1, 2, 3, or 4; a human T-celllymphotropic virus (HTLV) such as HTLV type I or II; a togaviruses suchas rubella virus, yellow fever virus, or sinbis virus; ebola virus; or acoronavirus such as severe acute respiratory syndrome (SARS) virus. Theenvelope virus can be any type or any strain of a given envelope virus.Non-limiting examples of envelope viruses and various types aredescribed herein.

In one embodiment, the envelope virus is a human immunodeficiency virus(HIV). In other embodiments, the envelope virus is a human herpes virus(e.g., HHV1 or HHV2 for the treatment of Herpes labialis and Herpesgenitalis), a hepatitis virus, a pox virus, an influenza virus, aparainfluenza virus, or a human T-cell lymphotropic virus (HTLV).

In some embodiments, the composition used in the methods is formulatedas a cream, gel, or lubricant.

For vaginal birth applications, the composition is administered to thebirth canal of the pregnant individual before birth. For example, thecomposition can be administered to the birth canal at least 1, 2, 3, 4,5, 6, 12, 24, 48, 72, or more hours before birth. In some examples, thecomposition is administered to the birth canal less than 72, 48, 24, 12,6, 5, 4, 3, 2, or 1 hour before birth. In some embodiments, a pluralityof administrations of the composition are applied to the birth canalwithin a period of one week prior to the birth. For example, a pluralityof administrations of the composition can applied to the birth canalwithin a period of 24, 12, or 6 hours prior to the birth.

Some embodiments of the methods described herein contain an additionalstep of administering to the individual an amount of an antimicrobialagent, e.g., antiviral agent, effective to reduce load of microorganism,e.g., virus, in the peripheral blood of the individual. Examples ofantiviral agents (e.g., anti-HIV agents) include a nucleoside reversetranscriptase inhibitor, a non-nucleoside reverse transcriptaseinhibitor, a protease inhibitor, a fusion inhibitor, and an integraseinhibitor.

Some embodiments of the methods described herein contain an additionalstep of intravenously administering to the individual prior to the birthan amount of a cholesterol-sequestering agent effective to reduce viralload in the individual.

In some embodiments, after cutting of the umbilical cord a newborn iscontacted with an amount of the cholesterol-sequestering agent effectiveto reduce or prevent transmission of the microorganism to the newborn.In addition, the cholesterol-sequestering agent can be administered tothe newborn orally and/or intravenously. In some instances thecholesterol-sequestering agent is administered to the fetusintravenously before birth.

In another aspect, the invention features a method of treating blood ora blood product. The method includes the steps of: providing a samplecontaining blood or a blood product; and contacting the sample in vitrowith a composition containing an amount of a cholesterol-sequesteringagent effective to reduce the load of a microorganism, if present, inthe sample, wherein the sample is maintained after the contacting stepin a sterile vessel.

The term “blood product” refers to a therapeutic material made fromblood and includes both blood components and plasma fractions.

The cholesterol-sequestering agent can be any of the compounds describedherein, e.g., a beta-cyclodextrin such as 2-OH-propyl-beta-cyclodextrin.

The microorganism can be any of the microorganisms described herein. Forexample, the microorganism can be an envelope virus such as a humanimmunodeficiency virus (HIV). In other embodiments, the microorganism isan envelope virus such as a human herpes virus, a hepatitis virus, a poxvirus, an influenza virus, a parainfluenza virus, a human T-celllymphotropic virus (HTLV), a West Nile virus, or a SARS virus.

The sample can contain, for example, whole blood, e.g., human wholeblood; plasma; serum; enriched red blood cells; enriched platelets; orprotein (e.g., an immunoglobulin or clotting factor) purified from wholeblood.

In some embodiments, the method includes an additional step ofintroducing the sample into an individual following the contacting ofthe sample with the composition.

In some embodiments, the method includes an additional step of removingor depleting white blood cells from the sample prior to introducing thesample into the individual.

The sample can optionally be identified as containing an envelope virus.

In some embodiments, the method includes an additional step of testingthe sample for the presence of the envelope virus following thecontacting with the composition.

In another aspect, the invention features a composition containing acholesterol-sequestering agent and an amount of blood or a blood productsuitable for administration to an individual having a blood-relateddisorder or deficiency, wherein the composition is maintained in asterile vessel.

The composition can contain, for example, whole blood, e.g., human wholeblood; plasma; serum; enriched red blood cells; enriched platelets; orprotein (e.g., an immunoglobulin or clotting factor) purified from wholeblood.

The composition (e.g., a composition containing whole blood) canadditionally contain an agent, such as an anticoagulant, that promotesthe storage of the blood or blood product. In some embodiments, thecomposition is frozen.

Unless otherwise defined, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this invention belongs. Although methods and materialssimilar or equivalent to those described herein can be used in thepractice or testing of the present invention, the exemplary methods andmaterials are described below. All publications, patent applications,patents, and other references mentioned herein are incorporated byreference in their entirety. In case of conflict, the presentapplication, including definitions, will control. The materials,methods, and examples are illustrative only and not intended to belimiting.

Other features and advantages of the invention will be apparent from thefollowing detailed description, and from the claims.

DETAILED DESCRIPTION

The present invention provides methods and compositions for preventingan infection by microorganisms such as envelope viruses. The methods andcompositions of the invention make use of a cholesterol-sequesteringagent that can have one or more of several possible effects on amicroorganism. For some microorganisms such as envelope viruses, acholesterol-sequestering agent may cause the lysis of the virus. Byremoving cholesterol from a viral membrane, a cholesterol-sequesteringagent not only disrupts the ordered structure of membrane elements, butfurther destroys the integrity of the membrane itself leading todisruption of the viral membrane and leakage of viral contents, anirreversible process that inactivates the viral particle. Accordingly, acholesterol-sequestering agent can cause a direct reduction in viralload in a biological sample. In other instances, acholesterol-sequestering agent can block the fusion of a virus with theplasma membrane and/or block the budding of the virus from lipid raftson the membrane of the infected cell. In some instances, acholesterol-sequestering agent may block the uptake of an intracellularpathogen by blocking endocytosis in a cell. Accordingly, acholesterol-sequestering agent can be used to reduce or prevent maternalto fetal transmission of a microorganism and/or to reduce or eliminate amicroorganism present in a blood sample or a blood product.

Cholesterol-Sequestering Agent

Any cholesterol-sequestering agent can be used in the methods andcompositions described herein. A cholesterol-sequestering agent binds tocholesterol and extracts and depletes cholesterol from a biologicalmembrane, such as a plasma membrane or a membrane of an envelope virus.A cholesterol-sequestering agent preferentially extracts cholesterolfrom lipid rafts present in a biological membrane.

Examples of cholesterol-sequestering agents include compounds such ascyclodextrins, nystatin, and filipin. Cyclodextrins include bothnaturally occurring cyclodextrins, e.g., alpha, beta, and gammacyclodextrins, as well as derivatives of naturally occurringcyclodextrins. Non-limiting examples of derivatives of naturallyoccurring cyclodextrins include derivatives of beta cyclodextrin such ashydroxypropyl beta cyclodextrin, carboxy-methyl beta cyclodextrin, andmethyl beta cyclodextrin. For a detailed description on cyclodextrinsand derivatives thereof, see, e.g., Parrish, M. A. “Cyclodextrins—aReview.” Sterling Organics Ltd., Newcastle-Upon-Tyne, England; andcyclodex.com.

Beta cyclodextrin, a simple sugar ring structure containing seven alpha(1-4) glucopyranose units, has the ability to rapidly extractcholesterol from lipid rafts, thereby disrupting their ordered membranestructure. As a result of cholesterol removal, lipid rafts are dispersedin the plane of the membrane and the mechanisms responsible for entryand exit of envelop viruses from target cells are abolished.

Beta cyclodextrin has a particularly high affinity for cholesterol. Whenused at concentrations ranging from 5-100 mM,2-OH-propyl-beta-cyclodextrin removes membrane cholesterol withinminutes. At the molecular level, beta cyclodextrin resembles a toroid orcup-like structure with openings at both the top and bottom. The toroidstructure contains hydrophilic groups on the exterior surface andhydrophobic groups on the interior surface. The hydrophylic groupsconfer solubility in aqueous medium while the hydrophobic groups formthe hydrophobic pocket that binds the cholesterol.

Hydroxypropyl beta cyclodextrin is an example of a derivative of betacyclodextrin that can be used in the methods of the invention.Hydroxypropyl beta cyclodextrin is a partially substitutedpoly(hydroxpropyl)ether of beta cyclodextrin. The basic closed circularstructure of beta cyclodextrin is maintained in hydroxypropyl betacyclodextrin. The glycosidic oxygen forming the bond between theadjacent glucose monomers and the hydrogen atoms lining the cavity ofthe cyclodextrin impart an electron density and hydrophobic character tothe cavity. Organic compounds interact with the walls of the cavity toform inclusion complexes. The hydroxyl groups and the hydroxypropylgroups are on the exterior of the molecule and interact with water toprovide the increased aqueous solubility of the hydroxypropyl betacyclodextrin and the complexes made with the hydroxypropyl betacyclodextrin. For a detailed description of the structure ofhydroxypropyl beta cyclodextrin, see, e.g., Muller et al. (1986)“Hydroxypropyl-B-cyclodextrin derivatives: Influence of average degreeof substitution on complexing ability and surface activity” J. Pharm.Sci. 75.

Treatment of Blood and Blood Products

A cholesterol-sequestering agent can be used to treat blood or a bloodproduct to inactivate a microorganism such as an envelope viruscontained therein. In general, a sample containing blood or a bloodproduct is contacted in vitro with a composition containing an amount ofa cholesterol-sequestering agent effective to reduce the load of amicroorganism, if present, in the sample. In these methods, the sampleis generally maintained in a sterile environment that permits the laterintroduction of the blood or blood product into an individual.

A sample containing blood or a blood product can be treated according tothe methods described herein to inactivate a microorganism such as anenvelope virus, if present, in the sample. The methods can optionallyinclude an additional step of testing the sample for the presence of themicroorganism before and/or after the treatment with thecholesterol-sequestering agent.

In embodiments where testing for the microorganism is performed prior tocontacting the sample with a cholesterol-sequestering agent, the resultof the testing can be used as an indication as to whether the sampleshould subsequently be treated with the cholesterol-sequestering agent.For example, in the case of testing for an envelope virus, a “viruspositive” result can be used as an indication that the sample should betreated so as to inactivate the envelope virus in the sample.Alternatively, a “virus-positive” result can be used as an indicationthat the sample should be discarded and no attempt at decontaminationshould be made. According to such a method, a “virus-negative” resultcan constitute the result of a first screen of a sample, wherein onlyafter a sample first tests negative is it further contacted with acholesterol-sequestering agent. Such a two step procedure can provide anadditional layer of precaution for “virus-negative” blood so as toreduce the likelihood that a virus may evade a detection method andsubsequently infect a transfusion recipient. For example, in some casesan envelope virus may have recently infected a donor so that the virusin a blood sample provided by the donor may not be detectable accordingto some testing methods.

Aside from whole blood, a blood sample can be processed in a variety ofways to yield blood products that can be administered to an individual.For example, white blood cells can be removed from a blood sample (aprocess known as “leukoreduction”) to thereby remove a population ofcells that may be infected with a microorganism such as an envelopevirus. In addition to providing a potential vehicle for viral infection,the transfusion of white blood cells can induce reactions in a recipientincluding, fever, chills and immune reactions that limit theeffectiveness of subsequent transfusions. Leukoreduction generallyremoves greater than 99.9% of the white blood cells from cellular bloodcomponents (red cells and platelets). White blood cells can be removedfrom a blood sample by methods such as filtration (e.g.,nano-filtration), affinity adhesion, or specialized centrifugation.

In addition to leukoreduction, a variety of other procedures can becarried out on a blood sample to yield useful blood products. Forexample, a blood sample can be treated to isolate plasma (fresh frozenplasma), cryoprecipitate, serum, red blood cells (e.g., white bloodcell-depleted red blood cells), platelets (e.g., platelet concentrates),granulocytes, or protein components of the blood (e.g., fibrinogen,albumin, a clotting factor, or immunoglobulin). Clotting factors includeFactors I, II, V, VII, VIII, IX, X, XI, XII, and XIII, and VonWillebrand Factor.

Blood or a blood product is treated with a cholesterol-sequesteringagent and subsequently administered to an individual. The step ofcontacting the blood or blood product with the cholesterol-sequesteringagent can occur at any point during or after the isolation of a bloodsample from a donor. For example, a blood sample can be directlycollected into an isolation vessel (e.g., a plastic collection bag) thatcontains an amount of a cholesterol-sequestering agent effective toreduce the load of a microorganism, e.g., an envelope virus, in theblood sample. Alternatively, a cholesterol-sequestering agent can beadded to a blood sample following its collection (e.g., after a test isperformed to determine the presence or absence of an envelope virus),during the processing of the blood sample, or when the processing hasbeen completed. For example, a leukodepleted blood sample can becontacted with a cholesterol-sequestering agent before and/or after theleukodepletion step. In methods that involve the enrichment orpurification of a blood product (e.g., a cell or a protein), thecholesterol-sequestering agent can optionally be added after theenrichment or purification step. Purification of a blood product can beeither partial purification or purification to homogeneity. Thecholesterol-sequestering agent can remain with the blood or bloodproduct when it is introduced to a recipient.

The amount of a cholesterol-sequestering agent to be used in the methodsdescribed herein can vary according to the specificcholesterol-sequestering agent and the amount of microorganism that isto be inactivated. Routine methods can be carried out to determine theoptimal dosage of a cholesterol-sequestering agent to be applied to agiven sample and a given microorganism. For example, an assay thatmeasures virus infectivity can be used to determine the effect of agiven dose of a cholesterol-sequestering agent on that virus. Thosedoses that reduce or eliminate infectivity of the microorganism (e.g.,as measured by infection of the virus in an experimental host cell oranimal model) can be used to treat blood or blood products according tothe methods described herein.

Reduction or Prevention of Maternal to Fetal Transmission of an EnvelopeVirus

A cholesterol-sequestering agent can be used to reduce or preventmaternal to fetal transmission of a microorganism, such as an envelopevirus, that can occur during birth. In general, a composition containinga cholesterol-sequestering agent is administered to a pregnantindividual in an amount effective to reduce or prevent maternal to fetaltransmission of the microorganism. The cholesterol-sequestering agentcan prevent or reduce transmission of the microorganism resulting fromeither a vaginal birth or a cesarean section birth. The methodsdescribed herein can optionally include a step of diagnosing thepregnant individual as having an infection with the microorganism.

In those embodiments where a cholesterol-sequestering agent is used toprevent or reduce transmission of a microorganism resulting from avaginal birth, the cholesterol-sequestering agent is administered to thebirth canal in an amount effective to reduce or prevent maternal tofetal transmission of the microorganism. In general, thecholesterol-sequestering agent is administered prior to birth andremains present in the birth canal during birth. Thecholesterol-sequestering agent can be administered to any or all of theuterus cervix, vagina, and/or vulva in advance of the birth. Repeatedadministrations of the cholesterol-sequestering agent can optionally beapplied as part of a regimen to reduce the load of the microorganism inthe birth canal and maintain the microorganism load at low ornon-detectable levels at the time of birth. Maternal to fetaltransmission of a microorganism such as an envelope virus can resultfrom, for example, the presence of free viral particles and/or virallyinfected cells in cervical or vaginal secretions and/or in fluidsreleased following the rupture of fetal membranes.

The cholesterol-sequestering agent can optionally be administered incombination with or formulated as a component of a lubricant. Alubricant can assist in child birth by, for example, reducing thefrictional forces involved in dilation that can cause damage to maternaltissue and promote maternal to fetal transmission of a microorganism.

In those embodiments where a cholesterol-sequestering agent is used toprevent or reduce transmission of a microorganism resulting from acesarean section birth, the cholesterol-sequestering agent isadministered to the site of a surgical incision in an amount effectiveto reduce or prevent maternal to fetal transmission of themicroorganism. In general, the cholesterol-sequestering agent isadministered immediately after the incision for the cesarean section ismade. For example, the cholesterol-sequestering agent can be applieddirectly to the areas of contact between maternal tissues and fetaltissues.

In either a vaginal birth or a cesarean section birth, acholesterol-sequestering agent can be applied directly to the newbornimmediately after birth. For example, the cholesterol-sequestering agentcan be applied to an exposed tissue of the newborn such as the umbilicalcord. The application of a cholesterol-sequestering agent directly tothe newborn can contribute to the reduction or elimination of amicroorganism, e.g., viral particles, that may remain inmaternal-derived biological material.

Compositions Containing Cholesterol-Sequestering Agents

As detailed herein, by removing cholesterol from the membrane of amicroorganism such as an envelope virus, a cholesterol-sequesteringagent not only disrupts the ordered structure of the membrane elements,but further destroys the integrity of the membrane itself leading todisruption of viral membranes and leakage of viral contents into themedium, an irreversible process that can fully inactivate the viralparticle. In addition, a cholesterol-sequestering agent can block thefusion of a virus with the plasma membrane and/or block the budding ofthe virus from lipid rafts on the membrane of the infected cell.Accordingly, a cholesterol-sequestering agent can be used to reduce orprevent maternal to fetal transmission of a microorganism and/or toreduce or eliminate a microorganism present in a blood sample or a bloodproduct.

Envelope viruses that can be targeted using the methods and compositionsdescribed herein include, but are not limited to: a humanimmunodeficiency virus (HIV) such as HIV-1 or HIV-2; a human herpesvirus (HHV) such as HHV1, HHV2, HHV3, HHV4, HHV5, HHV6, HHV7, or HHV8; ahepatitis virus such as hepatitis B virus, hepatitis C virus, orhepatitis D virus; a pox virus such as a small pox virus or moUuscumcontagiosum virus; an orthomyxovirus such as an influenza virus types A,B, or C; a paramyxovirus such as a mumps virus or a parainfluenza virustype 1, 2, 3, or 4; a human T-cell lymphotropic virus (HTLV) such asHTLV type I or II; a togaviruses such as rubella virus, yellow fevervirus, or sinbis virus; ebola virus; or a coronavirus such as severeacute respiratory syndrome (SARS) virus.

In addition to envelope viruses, the methods and compositions describedherein can be used to reduce or prevent maternal to fetal transmissionof a variety of microorganisms, for example, a bacterium (e.g., anthraxor chlamydia), a mycobacterium (e.g., mycobacterium tuberculosis), avirus (an envelope or non-envelope virus, e.g., a protein coated virussuch as picorna virus), a fungus, or a protozoan.

The methods and compositions described herein can be used to preventclinical conditions that result from an infection by en envelope virus,including but not limited to AIDS (HIV infection), certain cancers(caused by HTLV types I and II), fever blisters or cold sores (Herpeslabialis; HHV1 infection), genital herpes (Herpes genitalis; HHV2infection), chicken pox (HHV3 infection), herpes zoster or shingles(HHV3 infection), mononucleosis (HHV4 infection), cytomegalovirusinfection (HHV infection), Kaposi's Sarcoma (HHV8 infection), Germanmeasles (rubella virus infection), or severe acute respiratory syndrome(SARS virus infection). These clinical conditions can result from theinfection of an individual with an envelope virus as a result ofmaternal to fetal transmission of the virus or from the administrationof blood or a blood product that is contaminated with an envelope virus.

A variety of compositions can be formulated to contain an amount of acholesterol-sequestering agent effective to reduce or preventtransmission of an envelope virus. In the case of compositions used toreduce or prevent maternal to fetal transmission of a virus, thecomposition can be formulated for administration to the birth canal. Thecholesterol-sequestering agent can be contained in, for example, creams,lotions, ointments, gels, lubricants, liquids, sprays, powders, orabsorbent materials.

A composition containing a cholesterol-sequestering agent can alsoinclude a pharmaceutically acceptable carrier. As used herein thelanguage “pharmaceutically acceptable carrier” includes solvents,dispersion media, coatings, antiviral agents, antibacterial agents,antifungal agents, isotonic and absorption delaying agents, and thelike, compatible with pharmaceutical administration. Supplementaryactive compounds can also be incorporated into the compositions.

Antimicrobial Compounds

The methods described herein to reduce or prevent maternal to fetaltransmission of an envelope virus can be used in combination with one ormore anti-microbial agents, e.g., antiviral agents or antibacterialagents. For example, a pregnant individual infected by a virus such asHIV can be treated with an anti-viral agent such as a nucleoside reversetranscriptase inhibitor, a non-nucleoside reverse transcriptaseinhibitor, a protease inhibitor, a fusion inhibitor, and/or an integraseinhibitor. The antiviral treatments can be carried out over a period ofdays, weeks, or months in advance of the birth. Such treatments can beused to reduce viral load in the individual at the time of birth.Accordingly, the effectiveness of the cholesterol-sequestering agenttreatments can be enhanced in a pregnant individual wherein viral loadhas already been reduced by a secondary mechanism.

OTHER EMBODIMENTS

While the invention has been described in conjunction with the detaileddescription thereof, the foregoing description is intended to illustrateand not limit the scope of the invention, which is defined by the scopeof the appended claims. Other aspects, advantages, and modifications arewithin the scope of the following claims.

1. A method of treating blood or a blood product, the method comprising: providing a sample comprising blood or a blood product; and contacting the sample in vitro with a composition comprising an amount of a cholesterol-sequestering agent effective to reduce the load of a microorganism, if present, in the sample, wherein the sample is maintained after the contacting step in a sterile vessel.
 2. The method of claim 1, wherein the cholesterol-sequestering agent is a cyclodextrin.
 3. The method of claim 2, wherein the cyclodextrin is a beta-cyclodextrin.
 4. The method of claim 3, wherein the beta-cyclodextrin is 2-OH-propyl-beta-cyclodextrin.
 5. The method of claim 1, wherein the microorganism is a virus.
 6. The method of claim 5, wherein the virus is an envelope virus.
 7. The method of claim 6, wherein the envelope virus is a human immunodeficiency virus (HIV).
 8. The method of claim 6, wherein the envelope virus is a human herpes virus.
 9. The method of claim 6, wherein the envelope virus is a hepatitis virus.
 10. The method of claim 6, wherein the envelope virus is a pox virus.
 11. The method of claim 6, wherein the envelope virus is an influenza or a parainfluenza virus.
 12. The method of claim 6, wherein the envelope virus is a human T-cell lymphotropic virus (HTLV).
 13. The method of claim 1, wherein the microorganism enters a cell of a host by endocytosis during at least a portion of its life cycle.
 14. The method of claim 13, wherein the microorganism is a bacterium.
 15. The method of claim 13, wherein the microorganism is a mycobacterium.
 16. The method of claim 13, wherein the microorganism is a fungus.
 17. The method of claim 13, wherein the microorganism is a protozoan.
 18. The method of claim 1, wherein the sample comprises whole blood.
 19. The method of claim 18, wherein the whole blood is human whole blood.
 20. The method of claim 19, further comprising introducing the sample into an individual following the contacting of the sample with the composition.
 21. The method of claim 20, further comprising removing or depleting white blood cells form the sample prior to introducing the sample into the individual.
 22. The method of claim 6, wherein the sample is identified as containing an envelope virus.
 23. The method of claim 6, further comprising testing the sample for the presence of the envelope virus following the contacting with the composition.
 24. The method of claim 1, wherein the sample comprises plasma.
 25. The method of claim 1, wherein the sample comprises serum.
 26. The method of claim 1, wherein the sample comprises enriched red blood cells.
 27. The method of claim 1, wherein the sample comprises enriched platelets.
 28. The method of claim 1, wherein the sample comprises a protein purified from whole blood.
 29. A composition comprising a cholesterol-sequestering agent and an amount of blood or a blood product suitable for administration to an individual having a blood-related disorder or deficiency, wherein the composition is maintained in a sterile vessel.
 30. The composition of claim 29, wherein the composition comprises whole blood.
 31. The composition of claim 30, wherein the whole blood is human whole blood.
 32. The composition of claim 29, wherein the composition comprises plasma.
 33. The composition of claim 29, wherein the composition comprises serum.
 34. The composition of claim 29, wherein the composition comprises enriched red blood cells.
 35. The composition of claim 29, wherein the composition comprises enriched platelets.
 36. The composition of claim 29, wherein the composition comprises a protein purified from whole blood.
 37. The composition of claim 29, further comprising an agent that promotes the storage of the blood or blood product.
 38. The composition of claim 37, wherein the composition comprises whole blood.
 39. The composition of claim 38, wherein the agent is an anticoagulant.
 40. The composition of claim 39, wherein the composition is frozen.
 41. The composition of claim 29, wherein the composition comprises a purified immunoglobulin.
 42. The composition of claim 29, wherein the composition comprises a purified clotting factor. 